Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial.

STUDY OBJECTIVE: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer. DESIGN: A long-term follow-up of patients enrolled in a randomized trial. SETTING: The initial trial was performed in a tertiary care hospital in Beijing, China. PARTICIPANTS: Patients aged 60 years or older who were scheduled for major noncardiac surgery. INTERVENTION: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 µg/kg over 10 min, followed by a continuous infusion of 0.5 µg/kg/h until 1 h before end of surgery) or placebo during anesthesia. MEASUREMENTS: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis. RESULTS: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients. CONCLUSIONS: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases: Mendelian Randomization Study.

BACKGROUND: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. METHODS: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. RESULTS: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. CONCLUSION: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Integration analysis of GWAS and expression quantitative trait loci to identify candidate genes and pathways for clozapine-related neutropaenia.

AIMS: Little is known about the genetic basis of clozapine-related neutropaenia. This study aims to explore candidate genes and pathways involved in clozapine-related neutropaenia. METHODS: This study conducted a two-stage integrative analysis of the summary statistics from the genome-wide association study (GWAS, n = 552) of the lowest absolute neutrophil count (ANC) during clozapine treatment and the summary data of the expressed quantitative trait locus (eQTL). First, we use the probabilistic Mendelian randomization (PMR-Egger) to identify genes whose expression is causally related to ANC, and then use Bayesian co-localization analysis to investigate whether there are shared causal variants between them [posterior probability for hypotheses 4 (PP.H4) > 0.80]. Finally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore the pathways that may be associated with ANC during clozapine treatment. RESULTS: PMR-Egger analysis identified 146 genes that may be causally associated with ANC after Bonferroni correction (P-value < 3.25e-6). Bayesian co-localization analysis identified six further genes whose gene expression shared common variants with ANC, including NT5E (PP.H4 = 0.96), GLDC (PP.H4 = 0.82), NUDT17 (PP.H4 = 0.88), MSH4 (PP.H4 = 0.88), PTER (PP.H4 = 0.89) and SERPINB6 (PP.H4 = 0.83). Enrichment analysis identified 52 GO terms and seven pathways associated with ANC, such as NAD metabolic process, drug catabolic process and glyoxylate and dicarboxylate metabolism. CONCLUSION: This study identified multiple candidate genes and pathways that may be involved in clozapine-related neutropaenia, providing novel clues for the mechanism of clozapine-related neutropaenia.

Identifying causality, genetic correlation, priority and pathways of large-scale complex exposures of breast and ovarian cancers.

BACKGROUND: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. METHODS: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. RESULTS: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. CONCLUSIONS: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

The effect of dexmedetomidine on intraoperative blood glucose homeostasis: secondary analysis of a randomized controlled trial.

PURPOSE: To investigate the effect of dexmedetomidine on intraoperative blood glucose hemostasis in elderly patients undergoing non-cardiac major surgery. METHODS: This was secondary analysis of a randomized controlled trial. Patients in dexmedetomidine group received a loading dose dexmedetomidine (0.6 µg/kg in 10 min before anaesthesia induction) followed by a continuous infusion (0.5 µg/kg/hr) till 1 h before the end of surgery. Patients in control group received volume-matched normal saline at the same time interval. Primary outcome was the incidence of intraoperative hyperglycemia (blood glucose higher than 10 mmol/L). RESULTS: 303 patients in dexmedetomidine group and 306 patients in control group were analysed. The incidence of intraoperative hyperglycemia showed no statistical significance between dexmedetomidine group and control group (27.4% vs. 22.5%, RR = 1.22, 95%CI 0.92-1.60, P = 0.167). Median value of glycemic variation in dexmedetomidine group (2.5, IQR 1.4-3.7, mmol) was slightly lower than that in control group (2.6, IQR 1.5-4.0, mmol), P = 0.034. In multivariable logistic analysis, history of diabetes (OR 3.007, 95%CI 1.826-4.950, P < 0.001), higher baseline blood glucose (OR 1.353, 95%CI 1.174-1.560, P < 0.001) and prolonged surgery time (OR 1.197, 95%CI 1.083-1.324, P < 0.001) were independent risk factors of hyperglycaemia. CONCLUSIONS: Dexmedetomidine presented no effect on intraoperative hyperglycemia in elderly patients undergoing major non-cardiac surgery. TRIAL REGISTRATION: Present study was registered at Chinese Clinical Trial Registry on December 1, 2015 ( www.chictr.org.cn , registration number ChiCTR-IPR-15007654).

The diagnostic threshold of Cornell assessment of pediatric delirium in detection of postoperative delirium in pediatric surgical patients.

BACKGROUND: Cornell assessment of pediatric delirium (CAPD) showed advantage in diagnosis of pediatric delirium in Chinese critically ill patients. But its performance in surgical patients is still unclear. The present study was designed to validate the diagnostic performance of CAPD in surgical pediatric patients. METHODS: This is a prospective validation study. Pediatric patients who underwent selective surgery and general anesthesia were enrolled. Primary outcome was the incidence of delirium within postoperative three days. CAPD Chinese version was used to evaluate if the patient had delirium one time per day. At the meantime, a psychiatrist employed Diagnostic and Statistical Manual of Mental Disorders fifth edition to diagnose delirium, which was the "gold standard", and the result was considered as reference standard. Sensitivity, specificity and area under receiver operating characteristic (ROC) curve were calculated to investigate the performance of CAPD. RESULTS: A total of 170 patients were enrolled. Median age was 4 years old. As diagnosed by psychiatrist, 23 (13.5 %) patients experienced at least one episode of delirium during the follow-up period. When diagnostic threshold was set at 9, CAPD showed the optimal sensitivity (87.0 %, 95 %CI 65.3 %-96.6 %) and specificity (98.0 %, 95 %CI 93.7 %-99.5 %) in comparison with other diagnostic thresholds. ROC analysis showed that CAPD was a good delirium assessment instrument with area under curve of 0.911 (95 % CI 0.812 to 1.000, P < 0.001). Agreement between CAPD and reference standard was 0.849 (Kappa coefficient, P < 0.001). CONCLUSIONS: This study found that Cornell assessment of pediatric delirium could be used as an effective instrument in diagnosis of delirium in pediatric surgical patients. TRIAL REGISTRATION: www.chictr.org.cn Identifier: ChiCTR-DDD-17,012,231, August 3, 2017.

Antihypertensive medication adherence and cardiovascular disease risk: A longitudinal cohort study.

BACKGROUND AND AIMS: Few studies estimated the impact of antihypertensive adherence on cardiovascular diseases (CVD) in a longitudinal cohort with presence of time-dependent confounders. This study aims to assess the association between antihypertensive adherence and CVD using marginal structural Cox model (MSM-Cox) and to characterize blood pressure (BP) trajectories of patients with different adherence. METHODS: This longitudinal study included 16,896 hypertensive patients receiving antihypertensive medication. The median follow-up time was 3.5 years (25th to 75th, 1.75-4.75 years). BP and medication adherence were measured four times every year. We used MSM-Cox and Cox model to assess association between antihypertensive adherence and CVD events. The linear mixed-effects model was used to characterize BP trajectories of patients with different adherence, and the area under curves (AUC) was calculated as BP burden. RESULTS: We documented 4735 CVD events, crude incidence of CVD was 80.8 (95% CI, 78.1-83.4) and 112.6 (95% CI, 107.2-118.0) per 1000 person-years for baseline high-adherence and low-adherence, respectively. Compared with high adherence, the adjusted hazard ratio (HR) for association between low adherence with CVD was 1.75 (95%CI, 1.62-1.89) and 1.34 (95%CI, 1.26-1.42) based on the MSM-Cox and the Cox model, respectively. The BP burden and fluctuation range of BP trajectory in low-adherence patients were larger than those of high-adherence patients. Patients with high adherence got 28% greater reduction of BP burden than low-adherence patients. CONCLUSIONS: Antihypertensive adherence was more strongly associated with the risk of CVD than conventional regression analyses based on a single adherence measurement.

Climate change versus land-use change-What affects the ecosystem services more in the forest-steppe ecotone?

The Ecosystem services (ESs), which play an important role in the balance of the natural ecosystem and social-economic development, are suffering from degradation caused by human activities and climate change. However, the manner in which the ESs respond to the land use/cover changes (LUCCs) and the climatic factors respectively remain elusive, especially in the forest-steppe ecotone, which is highly sensitive to climate change and anthroponotic activities. Based on the remote sensing data and in situ meteorological data, we comprehensively modeled and compared 4 key ESs changes caused by 3 LUCC types, land-use change fraction, and climate changes through two simple comparative experiments. Our results showed that: the Grain for the Green Project improved the mean soil conservation, carbon sequestration, and water yield but reduced the sand fixation. The cropland expansion had a positive influence on the water yield and sand fixation, but it induced a decline in soil conservation and carbon sequestration. The urbanization very likely increased the water yield and decreased soil conservation, carbon sequestration, and sand fixation. The unequal change fractions of the same land-use conversion may affect the ESs differently. The ESs changes have different responses to climate change in different landscapes due to the ecological process. The water yield could be well explained by the temperature, precipitation, radiation, and wind speed. Climate change had a stronger effect on the water yield and carbon sequestration than the land use/cover changes but sand fixation and soil conservation were more likely to be affected by LUCCs. The impact of three types of land-use changes and climate change on the ecosystem services should be considered when formulating land-use policies. This paper might aid the decision-makers in achieving ESs sustainable management and develop land-use strategies in the forest-steppe ecotone.

Causal Pathways from Body Components and Regional Fat to Extensive Metabolic Phenotypes: A Mendelian Randomization Study.

OBJECTIVE: The aim of this study was to explore the causal effects and pathways from body components to extensive metabolic phenotypes. METHODS: Summarized data including 24 metabolic phenotypes from 10 consortiums were used to perform univariate, multivariable, and bidirectional Mendelian randomization analysis based on the network design. RESULTS: For metabolically related biomarkers, a 1-SD increase in body fat mass (BFM) was robustly associated with increased fasting insulin, systolic blood pressure, diastolic blood pressure, and urate and decreased high-density lipoprotein cholesterol levels. For metabolically related diseases, the odds ratios and 95% CIs of a 1-SD increase in BFM were 1.76 (1.37 to 2.25) for type 2 diabetes mellitus (T2DM), 1.11 (1.09 to 1.13) for hypertension, 1.40 (1.25 to 1.57) for coronary artery disease, 1.41 (1.25 to 1.59) for myocardial infarction, 1.25 (1.12 to 1.40) for ischemic stroke, and 1.62 (1.02 to 2.57) for gout. The effects of body fat on diseases were mediated by extensive intermediate biomarkers, including blood pressure, lipids, glycemic traits, and urate. Regional fats had a similar effect with body fat in both absolute and relative scales, whereas fat-free components increased only the risk of T2DM 1.73 (1.11 to 2.68) and chronic kidney disease 1.51 (1.11 to 2.06). CONCLUSIONS: Several potential pathways were found and confirmed the tremendous benefits of fat-lowering measures, including lowering of various regional fats. Future policies or interventions should focus more on the role of body fat.

The sensitivity and specificity of statistical rules for diagnosing delayed neurocognitive recovery with Montreal cognitive assessment in elderly surgical patients: A cohort study.

Delayed neurocognitive recovery (DNR) is common in elderly patients after major noncardiac surgery. This study was designed to investigate the best statistical rule in diagnosing DNR with the Montreal cognitive assessment (MoCA) in elderly surgical patients.This was a cohort study. One hundred seventy-five elderly (60 years or over) patients who were scheduled to undergo major noncardiac surgery were enrolled. A battery of neuropsychological tests and the MoCA were employed to test cognitive function at the day before and on fifth day after surgery. Fifty-three age- and education-matched nonsurgical control subjects completed cognitive assessment with the same instruments at the same time interval. The definition of the international study of postoperative cognitive dysfunction (ISPOCD 1) was adopted as the standard reference for diagnosing DNR. With the MoCA, the following rules were used to diagnose DNR: the cut-off point of ≤26; the 1 standard deviation decline from baseline; the 2 scores decline from baseline; and the Z score of ≥1.96. The sensitivity and specificity as well as the area under receiver operating characteristic curve for the above rules in diagnosis of DNR were calculated.The incidence of DNR was 13.1% (23/175) according to the ISPOCD1 definition. When compared with the standard reference, the 2 scores rule showed the best combination of sensitivity (82.6%, 95% confidence interval [CI] 67.1%-98.1%) and specificity (82.2%, 95% CI 76.2%-88.3%); it also had the largest area under receiver operating characteristic curve (0.824, 95% CI 0.728-0.921, P < .001). The cut-off point rule showed high sensitivity (95.7%) and low specificity (37.5%), whereas the 1 standard deviation and the Z score rules showed low sensitivity (47.8% and 21.7%, respectively) and high specificity (93.4% and 97.3%, respectively).Compared with the ISPOCD1 definition, the 2 scores rule with MoCA had the best combination of sensitivity and specificity to diagnose DNR.

Roles for circulating polyunsaturated fatty acids in ischemic stroke and modifiable factors: a Mendelian randomization study.

BACKGROUND: Available data about the effects of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its main risk factors remains limited and conflicting. Therefore, we conducted Mendelian randomization (MR) to assess whether genetically predicted PUFA affected IS, lipids and blood pressure (BP). METHODS: Genetic instruments associated with IS were derived from ISGC Consortium (n = 29,633), with lipids were derived from GLGC(n = 188,577), with BP were derived from Neale Lab(n = 337,000). The inverse-variance weighted method was the main analysis to estimate the effect of exposure on outcome. Sensitivity analyses included principal components analysis, MR-Egger, weighted median, and weighted mode. RESULTS: Per SD increases in serum α-linolenic acid (ALA) were associated with lower IS risk, with odd ratio (OR) of 0.867(0.782,0.961), arachidonic acid (AA) were associated with higher IS risk (OR: 1.053(1.014,1.094)). Likewise, Per SD increases in ALA were associated with the lower-level low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) (ß:-0.122(- 0.144, - 0.101), - 0.159(- 0.182, - 0.135), - 0.148(- 0.171, - 0.126), respectively), AA were associated with the higher-level of LDL-C, HDL-C and TC (ß:0.045(0.034,0.056), 0.059(0.050,0.067), 0.055(0.046,0.063), respectively). Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) had little or no association with IS, lipids or BP at Bonferroni-corrected significance. Different analytic methods supported these findings. The intercept test of MR-Egger implied no pleiotropy. CONCLUSIONS: High-level plasma ALA was protective for IS but AA was the opposite. LA, EPA, DHA, and DPA had no effects on IS.

Exploring Connections among Ecosystem Services Supply, Demand and Human Well-Being in a Mountain-Basin System, China.

Stakeholder perception and supply-demand relations are the main challenges and future directions for research on ecosystem services (ES). Based on spatial data and statistical data, we mapped eight key ES supply between 2005-2015 in the Huailai mountain-basin area. Using data from 507 survey questionnaires, we identified the ES demand and the public perceptions of the changes in ES. In addition, we also reveal the characteristics of the spatial distribution of ES demand, analyze the spatial supply-demand matching of ES, and explore the relationships between ES supply-demand and human well-being. From 2005 to 2015, a general upward trend was observed in the supply of four types of product provisioning services, which is different from the trend perceived by the stakeholders. An increasing trend was observed for carbon sequestration and forest recreation, which was in line with the perceptions of change. A spatial mismatch existed between the ES demand and supply, whereby the supply of carbon sequestration, soil conservation, habitat quality, and forest recreation services exceeded the demand in townships in the mountainous and hilly regions. On the other hand, townships located in the valley plains experienced a high imbalance between the demand and the supply. For the four types of product provisioning services, most towns and villages showed a balance in demand and supply. Linking ES supply-demand and human well-being showed that a threshold may exist in the supply-demand imbalance of regulating and supporting services before it begins to impact human well-being. Our study would enrich the theory and methodology research on relationships between ecosystem services and human well-being, and support knowledge to land allocation and management.

Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study.

Background: The causal evidence of the triglyceride-glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking. Methods: A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive control, and external verification were utilized. Outcomes include major outcomes [overall CVD, ischemic heart diseases (IHD), and cerebrovascular diseases (CED)] and minor outcomes [angina pectoris (AP), acute myocardial infarction (AMI), chronic IHD (CIHD), heart failure (HF), hemorrhagic stroke (HS), and ischemic stroke (IS)]. Results: The TyG index significantly increased the risk of overall CVD [OR (95% CI): 1.20 (1.14-1.25)], IHD [OR (95% CI): 1.22 (1.15-1.29)], CED [OR (95% CI): 1.14 (1.05-1.23)], AP [OR (95% CI): 1.29 (1.20-1.39)], AMI [OR (95% CI): 1.27 (1.16-1.39)], CIHD [OR (95% CI): 1.21 (1.13-1.29)], and IS [OR (95% CI): 1.22 (1.06-1.40)]. Joint exposure to genetically higher GLU and TG was significantly associated with a higher risk of overall CVD [OR (95% CI): 1.17 (1.12-1.23)] and IHD [OR (95% CI): 1.22 (1.16-1.29)], but not with CED. The effect of GLU and TG was independent of each other genetically and presented dose-response effects in bivariate meta-regression analysis. Conclusions: Lifelong genetic exposure to higher GLU and TG was jointly associated with higher cardiac metabolic risk while the TyG index additionally associated with several cerebrovascular diseases. The TyG index could serve as a more sensitive pre-diagnostic indicator for CVD while the joint GLU and TG could offer a quantitative risk for cardiac metabolic outcomes.

Methane emissions in grazing systems in grassland regions of China: A synthesis.

The effects of grazing on methane (CH4) budgets are important for understanding the balance of greenhouse gas emissions and removals in grassland ecosystems. However, the CH4 budgets of grazing systems, that is simultaneously considering CH4 uptake by grassland soils and emissions from ruminant enteric fermentation, livestock folds and animal feces, are poorly investigated, particularly for Chinese grasslands, and thus, remained unclear currently. Here, a synthesis of 43 individual studies was carried out to assess the grazing season/annual CH4 budgets and their responses to grazing in grassland ecosystems of China. The results showed that heavy grazing (HG) significantly decreased, while light grazing (LG) and moderate grazing (MG) had no significant effects soil CH4 uptake, as compared to un-grazing sites. Grazing has shifted Chinese grasslands from a sink to source for atmospheric CH4, and the grazing season/annual CH4 budgets increased with increasing grazing intensity, while the offset of CH4 uptake by grassland soils to total CH4 emissions from sheep, sheepfolds and feces were exponentially decreased with increasing grazing intensity. Moreover, the herbage biomass (HBM), organic matter intake (OMI) and live weight gain (LWG) were decreased while CH4 emission intensities (i.e., CH4 emission per HBM, OMI, and LWG) were linearly increased with increasing grazing intensity. Our results demonstrate that mediating grazing intensity, e.g., from HG to LG, could yield the optimal balance between maintaining productive grasslands and meanwhile mitigating CH4 emissions. This study could help for building strategies with implications for grassland management in China with similar CH4 emission problems.

Impact of dexmedetomidine infusion during general anaesthesia on incidence of postoperative delirium in elderly patients after major non-cardiac surgery: study protocol of a randomised, double-blinded and placebo-controlled trial.

INTRODUCTION: Delirium is a common complication in the elderly after surgery and is associated with worse outcomes. Multiple risk factors are related with postoperative delirium, such as exposure to general anaesthetics, pain and postoperative inflammatory response. Preclinical and clinical studies have shown that dexmedetomidine attenuated neurotoxicity induced by general anaesthetics, improved postoperative analgesia and inhibited inflammatory response after surgery. Several studies found that intraoperative use of dexmedetomidine can prevent postoperative delirium, but data were inconsistent. This study was designed to investigate the impact of dexmedetomidine administered during general anaesthesia in preventing delirium in the elderly after major non-cardiac surgery. METHODS AND ANALYSIS: This is a randomised, double-blinded and placebo-controlled trial. 620 elderly patients (age ≥60 years) who are scheduled to undertake elective major non-cardiac surgery (with an expected duration ≥2 hours) are randomly divided into two groups. For patients in the dexmedetomidine group, a loading dose dexmedetomidine (0.6 µg/kg) will be administered 10 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 µg/kg/hour until 1 hour before the end of surgery. For patients in the control group, normal saline will be administered with an identical rate as in the dexmedetomidine group. The primary endpoint is the incidence of delirium during the first five postoperative days. The secondary endpoints include pain intensity, cumulative opioid consumption and subjective sleep quality during the first three postoperative days, as well as the incidence of non-delirium complications and all-cause mortality within 30 days after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of Peking University First Hospital (2015-987) and registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn) with identifier ChiCTR-IPR-15007654. The results of the study will be presented at academic conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCRR-IPR-15007654; Pre-results.